Glia: the fulcrum of brain diseases

Abstract

Neuroglia represented by astrocytes, oligodendrocytes and microglial cells provide for numerous vital functions. Glial cells shape the micro-architecture of the brain matter; they are involved in information transfer by virtue of numerous plasmalemmal receptors and channels; they receive synaptic inputs; they are able to release 'glio'transmitters and produce long-range information exchange; finally they act as pluripotent neural precursors and some of them can even act as stem cells, which provide for adult neurogenesis. Recent advances in gliology emphasised the role of glia in the progression and handling of the insults to the nervous system. The brain pathology, is, to a very great extent, a pathology of glia, which, when falling to function properly, determines the degree of neuronal death, the outcome and the scale of neurological deficit. Glial cells are central in providing for brain homeostasis. As a result glia appears as a brain warden, and as such it is intrinsically endowed with two opposite features: it protects the nervous tissue as long as it can, but it also can rapidly assume the guise of a natural killer, trying to eliminate and seal the damaged area, to save the whole at the expense of the part. The sudden emergence of an intellect, and therefore a human being, which materialised only around a million years ago, remains the main mystery for our self-understanding. Similarly, we still do not know by which steps or transitions the human intellect emerged from the animal kingdom and where the fundamental difference between a man and an animal lies. According to the neuronal doctrine, which governs modern neuroscience since the beginning of the twentieth century, 1,2 the neurone is regarded as a basic information processing unit consisting of dendrites and axons with a unidirectional flow of information from the receiving dendrites via the integrating cell body to the terminal branches of the axon. Neuronal networks, connected through synaptic contacts, are generally considered as the substrate of our intellect.The number and size of neural cells increase with the size of the body and of the brain of mammals. This increasing quantity eventually has caused the generation of a new quality, the intellect. Rather amazingly, however, there is a relatively little difference in the morphology and physiology of neurones between humans and beasts; similarly the density of synaptic contacts in the brains of rodents and humans is more or less constant at around 1100-1300 millions/mm 3 . 3 On the contrary, evolution of the nervous system resulted in great changes in the second type of neural cells, the neuroglia. 4 Indeed, phylogenetic advance in brain complexity and capabilities coincided with a remarkable increase in the number of glial cells: in the rodent cortex the glial to neurone ratio is about 0.3 : 1, whereas in humans the same ratio is several times higher being B1.65:1, 5 while the total number of glial cells in the human brain is B10 (or even more) times larger than in lesser mammals. Astrocytes ...

Astrocytes in Alzheimer's Disease

“…114 Nonetheless, it is now clear that it is neuroglia, which determines the progression and outcome of most, if not all, neurological diseases. 115,116 Indeed, the brain homeostasis is managed solely by the neuroglia, and the failure of neuroglia to maintain this homeostasis is fatal for the nervous tissue. This is particularly manifest in the ischemic insult in which performance of astroglia very much determines the development of the ischemic core and its relations with penumbra.…”

Primary Neuron/Astrocyte Co‐Culture on Polyelectrolyte Multilayer Films: A Template for Studying Astrocyte‐Mediated Oxidative Stress in Neurons

“…The combination of these two polymers facilitated the patterning of co-cultures of primary neurons and astrocytes, thus allowing direct contact between the cells, more akin to the cellcell contact which exists in the brain than can be achieved with random co-cultures. [14][15][16][17] In addition, primary neurons were grown on various positive surfaces, such as (LPEI/ SPS) 10.5 and (BPEI/SPS) 10.5 , to evaluate whether the difference in cell adhesion and spreading was due to the electrostatic charge. Unlike the PDAC surfaces, primary neurons attached and spread on the positively charged LPEI and BPEI surfaces, suggesting that the electrostatic charge was not likely the mechanism for the difference in cell adhesion observed on the PDAC substrates.…”

“…[11][12][13] In this study, we used PEMs to pattern primary neurons and astrocytes to allow neuronal responses to be studied in the context of a complex cellular environment, namely, when in direct contact with astrocytes. [14][15][16][17] Cell-cell interactions are central to the function of many tissues, e.g., blood vessels form when endothelial cells are allowed to interact with smooth muscle cells [18] and nervous system function depends upon proper interactions between neuronal and glia cells. [19] The ability to mimic such interactions in vitro is important in cell biology studies as well as tissue engineering applications.…”

Janus a god with two faces: death and survival utilise same mechanisms conserved by evolution

“…Brain insults trigger reactive gliosis, which is a well conserved defence reaction; stronger insults, however, turn reactive glia into natural killers of neurones. 24 By this mechanism, glia saves the whole tissue at the expense of its injured part.…”

“…These guiding concepts have inspired the articles presented in this issue of Cell Death & Differentiation. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] This collection of reviews, dealing with mechanisms of cells and tissue damage and repair, is based on the invited lectures given at an international conference on this broad topic. This conference, which was organized jointly by Academia Europaea and The Klaus Tschira Foundation, took place in Heidelberg, Germany in March 2007 (Figure 1).…”